This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project focuses on the use of hyperpolarized 3He MRI for the systematic study of the structure and function of the lung in healthy and diseased human subjects. This project will also extend the methods of hyperpolarized gas production and imaging with the goal of making 3He MRI a more practical research and clinical tool. The most immediate objective is to characterize the progression of 3He imaging assessments over time and to identify which of those assessments have the potential to detect the early stages of Chronic Obstructive Pulmonary Disease (COPD). It will also attempt to apply a recently developed modality, imaging of the regional structure and function of the lung with hyperpolarized 3He MRI, to gain new insight into COPD progression. This technique will be used to track the evolution of pulmonary structure and function in 100 subjects over a period of five years. This project further plans to build on the skills gained over the past decade by using 3He MRI to obtain fundamentally new, detailed information about localized changes in the structure and gas- exchange efficiency of the lungs of subjects with clinically diagnosed COPD and subjects at risk for developing COPD (healthy smokers). The degree of COPD and study the progression of the disease using recently implemented methods for measuring the regional partial pressure of oxygen (PAO2) and the apparent diffusion coefficient (ADC) of hyperpolarized gas in vivo will be evaluated. As part of this project the change of these parameters in smokers who have not yet been diagnosed with lung disease will be monitored over time.